Mice lacking the Cβ subunit of PKA are resistant to angiotensin II-induced cardiac hypertrophy and dysfunction

Abstract

Background. PKA is a ubiquitous, multi-subunit cellular kinase that regulates a number of different physiological responses in response to cAMP, including metabolism, cell division, and cardiac function. Numerous studies have implicated altered PKA signaling in cardiac dysfunction. Recently, it has been shown that mice lacking the catalytic subunit of PKA (PKA C) are protected from age-related problems such as weight gain and enlarged livers, and we hypothesized that these mice might also be resistant to cardiomyopathy. Findings. Angiotensin II (ang II) induced hypertension in both PKA C null mice and their WT littermates. However, PKA C null mice were resistant to a number of ang II-induced, cardiopathological effects observed in the WT mice, including hypertrophy, decreased diastolic performance, and enlarged left atria. Conclusion. The C subunit of PKA plays an important role in angiotensin-induced cardiac dysfunction. The C null mouse highlights the potential of the PKA C subunit as a pharmaceutical target for hypertrophic cardiac disease. © 2010 Ladiges et al; licensee BioMed Central Ltd.